Cathepsin B in human myometrium and in uterine leiomyomas at various stages of tumour growth
Cathepsin B in human myometrium and in uterine leiomyomas at various stages of tumour growth
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DOI：
10.1016/j.ejogrb.2014.12.020
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发表时间：
2015-02-01
影响因子：
2.6
通讯作者：
Romanowicz, Lech
中科院分区：
文献类型：
--
作者：
Gogiel, Tomasz;Wolanska, Malgorzata;Romanowicz, Lech
目的：组织蛋白酶B是一种主要的半胱氨酸蛋白酶，参与细胞外基质蛋白的降解，也参与其他蛋白前体的激活和基质结合生长因子的释放。我们研究了组织蛋白酶B在人子宫肌层和子宫肌瘤中的表达和活性，以及半胱氨酸蛋白酶抑制剂在肿瘤生长不同阶段的抑制作用。研究设计：对12例患者的子宫肌层和不同重量的子宫肌瘤进行研究，其中小型(小于或等于25g，来自10例)和大型(大于或等于100g，来自13例)。用荧光底物检测组织提取液中组织蛋白酶B的活性和半胱氨酸蛋白酶抑制剂对木瓜酶的抑制作用，并计算每个DNA的含量。统计分析采用Kruskal-Wallis方差分析和Dunn‘s后处理检验。结果：在所研究的组织中，组织蛋白酶B主要以完全加工的双链形式存在。在对照子宫肌层和小肌瘤中，该酶的活性和表达相似。然而，在肿瘤生长过程中，它们明显增加。结论：组织蛋白酶B活性和表达的增强，而不是半胱氨酸蛋白酶抑制剂的作用，促进了细胞外基质的重塑和各种生长因子的生物利用度，从而促进了肌瘤的生长。(C)爱思唯尔爱尔兰有限公司出版的2015年。
Objective: Cathepsin B is a major cysteine protease involved in the degradation of extracellular matrix proteins, as well as in the activation of precursor forms of other proteases and in release of matrix-bound growth factors. We assessed the expression and activity of cathepsin B, and the inhibitory effect of cysteine protease inhibitors in human myometrium and uterine leiomyomas at various stages of tumour growth.Study design: Studies were performed on human myometrium collected from 12 patients and on uterine leiomyomas of various weights: small (less than or equal to 25 g, taken from 10 patients) and large (more than or equal to 100 g, obtained from 13 patients). Tissue extracts were assayed for cathepsin B activity and for inhibitory effect of cysteine protease inhibitors against papain using fluorogenic substrates, and calculated per DNA content. Statistical analysis was performed by Kruskal-Wallis analysis of variance followed by Dunn's post hoc tests. The enzyme expression was evaluated by SDS/polyacrylamide gel electrophoresis followed by Western immunoblotting.Results: In all the investigated tissues cathepsin B exists mainly in a fully processed double-chain form. The enzyme activity and expression were similar in control myometrium and in small leiomyomas. However, they distinctly increased during tumour growth. The effect of cysteine protease inhibitors was comparable in all the tissues examined.Conclusion: These data suggest that the enhanced activity and expression of cathepsin B but not the action of cysteine protease inhibitors contribute to an increased remodelling of extracellular matrix and bioavailability of various growth factors, which favour leiomyoma growth. (C) 2015 Published by Elsevier Ireland Ltd.